Subcutaneous Ofatumumab in Relapsing Remitting Multiple Sclerosis.

• Register: EUCTR
• Last refreshed on: 2 May 2016
• Main ID: EUCTR2011-002333-19-CZ
• Date of registration: 31/10/2011
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development Limited
• Public title: Subcutaneous Ofatumumab in Relapsing Remitting Multiple Sclerosis.
• Scientific title: A Randomized, Double-blind, Placebo controlled, Parallel-Group, Dose-Ranging Study to Investigate the MRI Efficacy and Safety of Six Months’ administration of Ofatumumab in Subjects with Relapsing-Remitting Multiple Sclerosis (RRMS) - Ofatumumab sub-cutaneous in RRMS
• Date of first enrolment: 27/02/2012
• Target sample size: 196
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002333-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 8

Countries of recruitment

Bulgaria, Canada, Czech Republic, Denmark, Germany, Italy, Netherlands, Norway, Russian Federation, Spain, United States

Contacts

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

• Name: GSK Clinical Support Helpdesk
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Able to provide signed, written informed consent to participate in the study
2. 18-55 years of age.
3. Definite diagnosis of MS according to the 2010 revisions of the McDonald
diagnostic criteria for MS [Polman, 2011].
4. Subjects do not have any manifestation of another type of MS other than RRMS.
5. Subjects must have a relapsing-remitting course of disease with at least one of the following prior to screening:
A. At least one confirmed relapse within the previous year or
B. At least two confirmed relapses within the previous 2 years or
C. At least one relapse in the previous 2 years, with a GdE brain lesion on an MRI scan in the past year.
6. Expanded Disability Status Scale (EDSS) score of 0-5.5 (inclusive) at screening.
7. Neurologically stable with no evidence of relapse for at least 30 days prior to start of Screening and during the Screening Phase (subjects who relapse during the screening
Phase can be re-screened, once the relapse has resolved).
8. A female subject is eligible to enter the study if she is:
A. Of non-childbearing potential
B. Of childbearing potential and NOT pregnant or nursing, has a negative serum pregnancy test at screening, and agrees to one of the following:
a. Complete abstinence from intercourse for the period from consent into the study until 6 months after the last dose of investigational product; or,
b. Consistent and correct use of one of the following acceptable methods of birth control for the period from consent into the study until 6 months after the last dose of investigational product:
i. Oral contraceptives (either combined or progesterone only)
ii. Injectable progesterone
iii. Levonorgestrel implants
iv. Estrogenic vaginal ring
v. Percutaneous contraceptive patches
vi. Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure
rate of <1% per year
vii. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject’s entry into the study; this male must be the sole partner for the subject
viii. Double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent
(foam/gel/film/cream/suppository).
A female is considered “Non-childbearing potential” if she is status-post hysterectomy, status-post surgical removal of both ovaries, has current, documented tubal ligation, or is postmenopausal and >2 years without menses. Female subjects who are post-menopausal <2 years must be confirmed menopausal by Follicle Stimulating Hormone (FSH) and
estradiol levels.
A female is considered “childbearing potential” if she has functional ovaries, ducts, and uterus with no impairment that would cause sterility. This includes women with oligomenorrhea (even severe), and women who are perimenopausal or who have just begun to menstruate.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 254
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects meeting any of the following criteria are not eligible and cannot enroll in the study:
1. Unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia,hypersensitivity to contrast media, or who lack adequate peripheral venous access).
2. Any clinically significant brain abnormality other than MS found on MRI.
3. Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) or confirmed PML (see Appendix 4, Section 11.4, for PML monitoring algorithm).
4. Subjects whom experience a relapse during the Screening Phase. These subjects may be eligible for re-screening after consultation with GSK.
5. History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral contusion, spinal cord compression) or a history or presence of myelopathy due to spinal cord compression by disk or vertebral disease.
6. Prior treatment with any of the following:
A. Systemic glucocorticoids or Adrenocorticotrophic hormone (ACTH) within one month prior to screening
B. Receipt of a live vaccine within 6 weeks prior to screening
C. Glatiramer acetate (Copaxone) or IFN-ß (Betaferon, Betaseron, Avonex, or Rebif) within 3 months prior to screening
D. Any immunomodulatory therapies, excluding glatiramer acetate or IFN-ß, within
6 months prior to screening including natalizumab and fingolimod (Gilenya),
immunoglobulin, or plasma exchange/plasmapheresis
E. Any monoclonal antibodies at any time, other than natalizumab (Tysabri)
F. Any lymphocyte-depleting therapies, including, but not limited to: cladribine, anti-CD4, total body irradiation, or bone marrow transplantation
G. Any immunosuppressive agents, including, but not limited to: mitoxantrone, azathioprine, cyclosporine, cyclophosphamide, or tacrolimus
7. Past or current history of medically significant adverse effects (including allergic reactions) from:
A. Cetirizine (or equivalent)
B. Paracetamol/acetaminophen
C. Corticosteroids
8. Known hypersensitivity to components of the investigational product.
9. Past or current malignancy, except for
A. Cervical carcinoma Stage 1B or less
B. Non-invasive basal cell and squamous cell skin carcinoma
C. Cancer diagnoses with a duration of complete response (remission) >5 years
D. A history of hematologic malignancy excludes a subject from participation,
regardless of response.
10. Electrocardiogram (ECG) showing a clinically significant abnormality at Screening
or showing an average QTcB or QTcF interval =450 msec (=480 msec for subjects with a Bundle Branch Block) over 3 consecutive ECGs.
11. Significant concurrent, uncontrolled medical condition including, but not limited to, cardiac, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency syndrome, pulmonary, cerebral, psychiatric, or neurological disease which in the opinion of the investigator could affect the subject’s safety, impair the subject’s reliable participation in the trial, impair the evaluation of endpoints, or necessitate the use of medication not allowed by this protocol.
12. History of severe, clinically significant CNS trauma (e.g. cerebral contusion, spinal cord compression) or a history or presence of myelopathy due to spinal cord compression by disk or vertebral disease.
13. Chronic or ongoing active infectious disease requiring long term systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, or active hepatitis

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Relapsing-Remitting Multiple Sclerosis (RRMS)
MedDRA version: 14.1 Level: LLT Classification code 10070716 Term: Multiple sclerosis pseudo relapse System Organ Class: 100000004852

Intervention(s)

Trade Name: Arzerra®
Product Name: Ofatumumab
Product Code: GSK1841157
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: OFATUMUMAB
CAS Number: 679818-59-8
Current Sponsor code: GSK1841157
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Cumulative number of new T1 gadolinium-enhancing brain lesions at Week 12 from Week 0 based on MRI scans at Weeks 4, 8, and 12.

Timepoint(s) of evaluation of this end point: Week 12

Secondary Objective: To evaluate the robustness of the MRI efficacy of ofatumumab 3, 30 or 60
milligrams (mg) given subcutaneously (SQ) over the 24 week treatment period relative to the first 12 weeks of the treatment period
• To evaluate the safety and tolerability over a period of 24 weeks of a range of SQ ofatumumab doses in subjects with RRMS
• To make a preliminary assessment of the efficacy of a range of SQ doses of ofatumumab in subjects with RRMS based on frequency of clinical relapses over a period of 24 weeks
• To determine the extent of B-cell depletion for a range of SQ doses of ofatumumab in subjects with RRMS
• To determine the extent of B-cell repletion following cessation of SQ ofatumumab treatment within specified time periods in subjects with RRMS
• To evaluate the immunogenicity of SQ ofatumumab in subjects with RRMS
For other study objectives please refer page12 of protocol.

Main Objective: To determine whether ofatumumab 3, 30 or 60 milligrams (mg) given subcutaneously (SQ), reduces the cumulative number of new T1 GdE brain lesions over a period of 12 weeks, as compared with placebo, in subjects with RRMS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12, Week 24, and/or Week 48

Secondary end point(s): •Cumulative number of new T1 Gd-enhancing brain lesions at Week 24 from Week 0 based on MRI scans at Weeks 4, 8, 12, 16, 20, and 24.
•Gd-enhancing brain lesions on T1-weighted MRI based on MRI scans at Weeks 4, 8, and 12:
-Cumulative number of persistent lesions at Week 12 from Week 0;
-Cumulative number of all lesions at Week 12 (new plus persistent) from Week 0;
-Total volume of new lesions at Week 12 (relative to Week 0);
-Total volume of all lesions (new plus persistent)
•T2 lesions based on MRI scans from Week 0 to Weeks 4, 8, and 12:
-Cumulative number of new and/or newly enlarging lesions at Week 12;
-Volume of new and/or newly enlarging T2 lesions at Week 12
•T1 hypointense lesions:
-Cumulative number of new T1 hypointense lesions at Week 24 and Week 48 from Week 0;
-Change from baseline in volume of T1 hypointense lesions at Week 24 and Week 48
•Change from baseline in brain volume at Week 24 and Week 48

Secondary ID(s)

2011-002333-19-DE

OMS112831

Source(s) of Monetary Support

Pharma R&D, GlaxoSmithKline Ltd.